Cognitive Impairment after Post-Acute COVID-19 Infection: A Systematic Review of the Literature

Abstract:

The present study aims to provide a critical overview of the literature on the relationships between post-acute COVID-19 infection and cognitive impairment, highlighting the limitations and confounding factors. A systematic search of articles published from 1 January 2020 to 1 July 2022 was performed in PubMed/Medline. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies using validated instruments for the assessment of cognitive impairment were included. Out of 5515 screened records, 72 studies met the inclusion criteria.

The available evidence revealed the presence of impairment in executive functions, speed of processing, attention and memory in subjects recovered from COVID-19. However, several limitations of the literature reviewed should be highlighted: most studies were performed on small samples, not stratified by severity of disease and age, used as a cross-sectional or a short-term longitudinal design and provided a limited assessment of the different cognitive domains. Few studies investigated the neurobiological correlates of cognitive deficits in individuals recovered from COVID-19. Further studies with an adequate methodological design are needed for an in-depth characterization of cognitive impairment in individuals recovered from COVID-19.

Source: Perrottelli A, Sansone N, Giordano GM, Caporusso E, Giuliani L, Melillo A, Pezzella P, Bucci P, Mucci A, Galderisi S. Cognitive Impairment after Post-Acute COVID-19 Infection: A Systematic Review of the Literature. J Pers Med. 2022 Dec 15;12(12):2070. doi: 10.3390/jpm12122070. PMID: 36556290; PMCID: PMC9781311. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781311/ (Full text)

COVID fog demystified

Abstract:

Acute mild respiratory SARS-CoV-2 infection can lead to a more chronic cognitive syndrome known as “COVID fog.” New findings from Fernández-Castañeda et al. reveal how glial dysregulation and consequent neural circuit dysfunction may contribute to cognitive impairments in long COVID.

Source: Kao J, Frankland PW. COVID fog demystified. Cell. 2022 Jul 7;185(14):2391-2393. doi: 10.1016/j.cell.2022.06.020. Epub 2022 Jun 15. PMID: 35768007; PMCID: PMC9197953. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197953/ (Full text)

Cognitive impairments in chronic fatigue syndrome patients: choice reaction time, encoding of new information, response organisation and selective attention

ABSTRACT:

Background: One of the features of Chronic Fatigue Syndrome (CFS) is the reporting of cognitive impairment. Prior research has confirmed this using cognitive performance test batteries. Psychomotor slowing and episodic memory impairments appear to be robust, but little is known about selective attention or the stages of processing leading to slower reaction times. The present study addressed these gaps in the literature.

Methods: CFS patients were recruited from a health service clinic. Sixty-seven patients agreed to carry out cognitive tasks measuring aspects of focused attention and categoric search and the components (encoding and response organisation) of choice reaction time. They were compared with 126 healthy controls. As well as carrying out the performance tasks, the participants also completed symptom checklists and questionnaires measuring fatigue, mental health and cognitive failures.

Results: The questionnaires revealed the typical profile of symptoms of CFS patients. With regards to the objective performance tasks, the CFS patients had significantly slower choice reaction times on both tasks. This is likely to be due to slower motor responses as neither of the measures of stimulus encoding or response organisation showed differences between the groups. There was also little evidence for the groups differing in aspects of selective attention.

Conclusions: CFS patients report greater fatigue, more somatic symptoms, greater mental health issues and more cognitive difficulties. Objective testing revealed slower choice reaction times which probably reflect motor slowing. These measures can now be used to assess the efficacy of the management of CFS.

Source: Smith AP. Cognitive impairments in chronic fatigue syndrome patients: choice reaction time, encoding of new information, response organisation and selective attention. World Journal of Pharmaceutical and Medical Research 8(4): 27-36 https://www.wjpmr.com/home/article_abstract/4110 (Full text available as PDF file)

Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome

Abstract:

Emerging evidence suggests that central nervous system dysfunction may underlie the core symptoms of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in adults, such as cognitive disturbance, fatigue and post-exertional malaise. Research into brain dysfunction in the pediatric CFS/ME context, however, is severely lacking. It is unclear whether the adolescent CFS/ME brain functions differently compared with healthy peers, particularly in situations where significant mental effort is required. This study used resting-state functional MRI in a novel repeated-measures design to evaluate intrinsic connectivity, cognitive function, and subjective fatigue, before and after a period of cognitive exertion in 48 adolescents (25 CFS/ME, 23 healthy controls).

Results revealed little evidence for a differential effect of cognitive exertion in CFS/ME compared with controls. Both groups demonstrated a similar rate of reduced intrinsic functional connectivity within the default mode network (DMN), reduced sustained attentional performance, slower processing speed, and increased subjective fatigue as a result of cognitive exertion.

However, CFS/ME adolescents consistently displayed higher subjective fatigue, and controls outperformed the CFS/ME group overall on cognitive measures of processing speed, sustained attention and new learning. No brain-behavior relationships were observed between DMN connectivity, cognitive function, and fatigue over time.

These findings suggest that effortful cognitive tasks may elicit similar levels of energy expenditure across all individuals in the form of reduced brain functioning and associated fatigue. However, CFS/ME may confer a lower starting threshold from which to access energy reserves and cognitive resources when cognitive effort is required.

Source: Josev EK, Malpas CB, Seal ML, Scheinberg A6, Lubitz L, Rowe K, Knight SJ. Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome. Brain Imaging Behav. 2019 May 17. doi: 10.1007/s11682-019-00119-2. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31102168

Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction

Abstract:

OBJECTIVES: To explore cognitive performance in chronic fatigue syndrome (CFS) examining two cohorts. To establish findings associated with CFS and those related to co-morbid depression or autonomic dysfunction.

METHODS: Identification and recruitment of participants was identical in both phases, all CFS patients fulfilled Fukuda criteria. In Phase 1 (n = 48) we explored cognitive function in a heterogeneous cohort of CFS patients, investigating links with depressive symptoms (HADS). In phase 2 (n = 51 CFS & n = 20 controls) participants with co-morbid major depression were excluded (SCID). Furthermore, we investigated relationships between cognitive performance and heart rate variability (HRV).

RESULTS: Cognitive performance in unselected CFS patients is in average range on most measures. However, 0-23% of the CFS sample fell below the 5th percentile. Negative correlations occurred between depressive symptoms (HAD-S) with Digit-Symbol-Coding (r = -.507, p = .006) and TMT-A (r = -.382, p = .049). In CFS without depression, impairments of cognitive performance remained with significant differences in indices of psychomotor speed (TMT-A: p = 0.027; digit-symbol substitution: p = 0.004; digit-symbol copy: p = 0.007; scanning: p = .034) Stroop test suggested differences due to processing speed rather than inhibition. Both cohorts confirmed relationships between cognitive performance and HRV (digit-symbol copy (r = .330, p = .018), digit-symbol substitution (r = .313, p = .025), colour-naming trials Stroop task (r = .279, p = .050).

CONCLUSION: Cognitive difficulties in CFS may not be as broad as suggested and may be restricted to slowing in basic processing speed. While depressive symptoms can be associated with impairments, co-morbidity with major depression is not itself responsible for reductions in cognitive performance. Impaired autonomic control of heart-rate associates with reductions in basic processing speed.

Source: Robinson LJ, Gallagher P, Watson S, Pearce R, Finkelmeyer A, Maclachlan L, Newton JL. Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction. PLoS One. 2019 Feb 5;14(2):e0210394. doi: 10.1371/journal.pone.0210394. eCollection 2019. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210394 (Full article)

Feedback on underperformance in patients with Chronic Fatigue Syndrome: The impact on subsequent neuropsychological test performance

Abstract:

Performance Validity Tests (PVTs) are used to measure the credibility of neuropsychological test results. Until now, however, a minimal amount is known about the effects of feedback upon noncredible results (i.e., underperformance) on subsequent neuropsychological test performance.

The purpose of this study was to investigate the effects of feedback on underperformance in Chronic Fatigue Syndrome (CFS) patients. A subset of these patients received feedback on Amsterdam Short-Term Memory (ASTM) failure (i.e., feedback [FB] group). After matching, the final sample consisted of two comparable groups (i.e., FB and No FB; both n = 33). At baseline and follow-up assessment, the patients completed the ASTM and two measurements of information processing speed (Complex Reaction Time [CRT] and Symbol Digit Test [SDT]).

Results indicated that the patients in the FB group improved significantly on the CRT, compared to the No FB group. Although not significant, a comparable trend-like effect was observed for the SDT. Independent of the feedback intervention there was a substantial improvement on ASTM performance at re-administration. A limited feedback intervention upon underperformance in CFS patients may result in improvement on information processing speed performance. This implies that such an intervention might be clinically relevant, since it maximizes the potential of examining the patients’ actual level of cognitive abilities.

Source: Roor JJ, Knoop H, Dandachi-FitzGerald B, Peters MJV, Bleijenberg G, Ponds RWHM. Feedback on underperformance in patients with Chronic Fatigue Syndrome: The impact on subsequent neuropsychological test performance. Appl Neuropsychol Adult. 2018 Oct 31:1-9. doi: 10.1080/23279095.2018.1519509. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30380922

Attention network test: assessment of cognitive function in chronic fatigue syndrome

Abstract:

Information processing difficulties are common in patients with chronic fatigue syndrome (CFS). It has been shown that the time it takes to process a complex cognitive task, rather than error rate, may be the critical variable underlying CFS patients’ cognitive complaints. The Attention Network Task (ANT) developed by Fan and colleagues may be of clinical utility to assess cognitive function in CFS, because it allows for simultaneous assessment of mental response speed, also called information processing speed, and error rate under three conditions challenging the attention system.

Comparison of data from two groups of CFS patients (those with and without comorbid major depressive disorder; n = 19 and 22, respectively) to controls (n = 29) consistently showed that error rates did not differ among groups across conditions, but speed of information processing did. Processing time was prolonged in both CFS groups and most significantly affected in response to the most complex task conditions. For simpler tasks, processing time was only prolonged in CFS participants with depression. The data suggest that the ANT may be a task that could be used clinically to assess information processing deficits in individuals with CFS.

© 2013 The British Psychological Society.

 

Source: Togo F, Lange G, Natelson BH, Quigley KS. Attention network test: assessment of cognitive function in chronic fatigue syndrome. J Neuropsychol. 2015 Mar;9(1):1-9. doi: 10.1111/jnp.12030. Epub 2013 Sep 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159443/ (Full article)

 

Cognitive deficits in chronic fatigue syndrome and their relationship to psychological status, symptomatology, and everyday functioning

Abstract:

OBJECTIVE: To examine cognitive deficits in people with chronic fatigue syndrome (CFS) and their relationship to psychological status, CFS symptoms, and everyday functioning.

METHOD: The current study compared the cognitive performance (reaction time, attention, memory, motor functioning, verbal abilities, and visuospatial abilities) of a sample with CFS (n = 50) with that of a sample of healthy controls (n = 50), all of whom had demonstrated high levels of effort and an intention to perform well, and examined the extent to which psychological status, CFS symptoms, and everyday functioning were related to cognitive performance.

RESULTS: The CFS group showed impaired information processing speed (reaction time), relative to the controls, but comparable performance on tests of attention, memory, motor functioning, verbal ability, and visuospatial ability. Moreover, information processing speed was not related to psychiatric status, depression, anxiety, the number or severity of CFS symptoms, fatigue, sleep quality, or everyday functioning.

CONCLUSION: A slowing in information processing speed appears to be the main cognitive deficit seen in persons with CFS whose performance on effort tests is not compromised. Importantly, this slowing does not appear to be the consequence of other CFS-related variables, such as depression and fatigue, or motor speed.

PsycINFO Database Record (c) 2013 APA, all rights reserved.

 

Source: Cockshell SJ, Mathias JL. Cognitive deficits in chronic fatigue syndrome and their relationship to psychological status, symptomatology, and everyday functioning. Neuropsychology. 2013 Mar;27(2):230-42. doi: 10.1037/a0032084. https://www.ncbi.nlm.nih.gov/pubmed/23527651

 

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma

Abstract:

The aim of this article is to provide a comprehensive and updated review of the key neuropsychiatric and neuropsychological complaints associated with chronic fatigue syndrome (CFS). Neuropsychiatric and neuropsychological difficulties are common in CFS and are linked primarily to disorders of mood, affect and behaviour.

The neuropsychiatric complaint most frequently encountered amongst CFS patients is depression and in particular major depressive disorder (MDD). Despite decades of research, the precise aetiological relationship between CFS and MDD remains poorly understood. This has resulted in the development of a number of interesting and polarised hypotheses regarding the aetiological nature of CFS. Recent scientific advances have however begun to unravel a number of interesting inflammatory and immunological explanations that suggest CFS and MDD are distinct yet interrelated conditions.

The possibility that the overlap between CFS and MDD might be explained in terms of shared oxidative and nitrosative (IO&NS) pathways is an area of intense research interest and is reviewed in detail in this article. The overlap between CFS and MDD is further differentiated by variations in HPA axis activity between the two disorders. Important immunological differences between MDD and CFS are also reviewed with particular emphasis on antiviral RNase L pathways in CFS.

In addition to the presence of neuropsychiatric complaints, CFS is also associated with neuropsychological symptoms such as impaired attention, memory and reaction time. The key neuropsychological problems reported by CFS patients are also included in the review in an effort to understand the significance of cognitive impairment in CFS.

 

Source: Christley Y, Duffy T, Everall IP, Martin CR. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013 Apr;15(4):353. doi: 10.1007/s11920-013-0353-8. https://www.ncbi.nlm.nih.gov/pubmed/23440559

 

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome

Abstract:

BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS.

METHODS: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between-group differences in autonomic reactivity and associations with cognitive performance were analysed.

RESULTS: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes.

CONCLUSIONS: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.

 

Source: Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U. Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. PLoS One. 2012;7(11):e49518. doi: 10.1371/journal.pone.0049518. Epub 2012 Nov 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498107/ (Full article)